Recruiting

Phase 3

Belantamab Mafodotin vs. DaratumumabBelantamab Mafodotin or Daratumumab With Bortezomib, Lenalidomide and Dexamethasone for Newly Diagnosed Multiple Myeloma

Sponsor:

PrECOG, LLC.

Code:

NCT07285239

Conditions

Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Arm A: Belantamab Mafodotin

Arm B: Daratumumab Hyaluronidase

Bortezomib

Lenalidomide

Dexamethasone

Study Details

Brief summary:

Eligible participants with newly diagnosed myeloma who are not considered eligible or refuse bone marrow transplant will be enrolled. Participants will be randomized to either belantamab mafodotin or daratumumab given in combination with bortezomib, lenalidomide and dexamethasone. Treatment will continue until disease progression, unacceptable side effects or withdrawal of consent.

Belantamab mafodotin is a targeted cancer treatment that works against multiple myeloma cells. It combines a homing device (an antibody) with a powerful cell-killing drug (a toxin), delivering the toxin directly to cancer cells while largely sparing healthy cells.

Minimal residual disease (MRD) testing will be done on bone marrow samples obtained standardly during your treatment. MRD shows whether a very small number of cancer cells can still be detected after treatment, even if standard lab tests shows no signs of cancer.

The purpose of this study is to evaluate if belantamab mafodotin, bortezomib, lenalidomide and dexamethasone (BVRd) improves minimal residual disease (MRD) negative status and/or prolongs progression-free survival (PFS) compared with daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) in participants with newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma

Study ID

NCT07285239

Start date

Sep, 2026

Status verified date

Aug, 2026

Completion date

Jun, 2034

Anticipated

Primary completion date

Nov, 2031

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Eligibility Criteria:

Patient must have suspected or confirmed newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria and must not have received more than one cycle of any myeloma treatment.
Patient must be considered ineligible for autologous stem cell transplantation by the treating physician because of their age (≥ 70 years) or aged 18 - 70 years with the presence of underlying medical conditions likely to have a negative impact on tolerability of high-dose chemotherapy with stem-cell transplantation, making them transplant ineligible, OR transplant-eligible and refusing stem-cell transplantation until first relapse or later.
Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to randomization.

≥ 1g/dL monoclonal protein (M-protein) on serum protein electrophoresis
Involved free light chain ≥ 10 mg/dL or ≥ 100 mg/L AND abnormal serum immunoglobulin kappa to lambda free light chain ratio (<0.26 or >1.65)
≥ 200 mg/24 hours of monoclonal protein on a 24-hour urine protein electrophoresis
Monoclonal bone marrow plasmacytosis ≥ 30% (evaluable disease)
Patient must be ≥ 18 years and <80 years of age.
Patient must have an Eastern Cooperative Group (ECOG) Performance Status (PS) of 0-2 (PS 3 allowed if secondary to pain).
Patient must have IMWG Frailty Score <2.
Patient must have the ability to understand and willingness to sign a written informed consent document.
Patient must be willing to provide bone marrow (aspirate and/or biopsy) and blood samples for determination of International Myeloma Society (IMS) risk status and for research. Indeterminate patients with missing or unevaluable samples will be excluded.
Patient must have received no more than one cycle (28 days or less) of prior chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma. Prior radiation therapy to symptomatic lesions is allowed provided there is no residual toxicity related to radiation and blood counts meet the study requirements. NOTE: Patients who have received prior treatment for smoldering multiple myeloma (SMM) are eligible.
Patient must have a Serum Protein Electrophoresis (SPEP), Urine Protein Electrophoresis (UPEP), and serum Free Light Chain (FLC) assay performed within 28 days prior to registration. In addition, a bone marrow biopsy and/or aspirate is required within 28 days prior to registration if measurable disease is only present in bone marrow. Otherwise, a bone marrow examination must have been performed within 90 days prior to registration.
Patient must have adequate organ function and marrow function as defined below, obtained ≤ 2 weeks prior to registration.

Absolute Neutrophil Count (ANC) ≥ 1000/microliter (mcL)
Platelets ˃75,000/mcL
Creatinine clearance (CrCl) ≥ 30 mL/min
Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3x upper limit of normal (ULN)
Total Bilirubin ≤ 1.5x ULN or ≤ 3x ULN for patients with documented Gilbert's disease
Patient must agree to register to the mandatory lenalidomide (Revlimid) Risk Evaluation and Mitigation Strategy (REMS) program and be willing and able to comply with the requirements of the REMS program.
Patient must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study, and for 3 months after the last dose of protocol treatment.
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Patient with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association (NYHA) Functional Classification. To be eligible for this trial, patient must be class 2 or better.
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Patients must not have peripheral neuropathy ≥ Grade 2 on clinical examination or Grade 1 with pain at time of registration.
Patients must not have any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Patient may have a history of current or previous deep vein thrombosis (DVT) or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation as prophylaxis if they are not currently on full-dose anticoagulation.
Patients must not have any known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients, or known sensitivity to mammalian-derived products.
Patients must not have current corneal epithelial disease except mild punctuate keratopathy.
Contact lenses must be avoided for participants while they are receiving belantamab mafodotin treatment unless cleared by an eye-care specialist. If cleared for use, bandaged contact lenses are specifically recommended. Contact lens use may be restarted after discontinuation of belantamab mafodotin treatment, provided the eye-care specialist confirms there are no other contraindications.
Patients must not have symptomatic amyloidosis or active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-proliferative disorder, skin changes) at the time of screening.
Patients must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol.

Study Design

Enrollment

500 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Belantamab Mafodotin

Belantamab mafodotin in combination with bortezomib, lenalidomide and dexamethasone (VRd) until progression, unacceptable toxicity or participant withdrawal. 1 cycle = 28 days.

active comparator: Arm B:

Daratumumab in combination with bortezomib, lenalidomide and dexamethasone (VRd) until progression, unacceptable toxicity or participant withdrawal. 1 cycle = 28 days.

Interventions

Arm A: Belantamab Mafodotin

1.9 milligram/kilogram (mg/kg) intravenous (IV) will be administered every 8 weeks for first 24 weeks (Cycles 1-3), then 1.9 mg/kg every 12 weeks (Cycles 4+) until progression, unacceptable toxicity or participant withdrawal

Arm B: Daratumumab Hyaluronidase

1800 mg subcutaneous (SC) will be administered weekly from Week 1-8 (Cycles 1 and 2), every 2 weeks from Week 9-24 (Cycles 3-6), and every 4 weeks from Week 25 (Cycles 7+) onwards until progression, unacceptable toxicity or participant withdrawal

Bortezomib

1.3 milligrams per square meter (mg /m²) SC on days 1, 8 and 15 of every 28 day bortezomib treatment cycle for 8 cycles

Lenalidomide

25 mg orally (PO) Days 1-21 of every 28 day lenalidomide treatment cycle.

Dexamethasone

40 mg PO on Days 1, 8, 15, and 22 of each 28-day cycle (may decrease to 20 mg if >75 years old)

Primary outcome measure

MRD Negative Status [ Time Frame: Up to 86 months ]
Progression-Free Survival (PFS) [ Time Frame: Up to 86 months ]

Central Contacts and Locations

Central contacts

Michael Wright, MS

267-319-3910 PrE1005@precogllc.org

Locations

Gundersen Lutheran

Recruiting

La Crosse, Wisconsin, United States, 54601

Contacts

Savannah Shallue

608-775-4113 savannah.shallue@emplifyhealth.org

Tory Borzyskowski

608-775-8521 tori.borzyskowski@emplifyhealth.org

Principal Investigator:

Yacki Hayashi-Tanner, MD

More Information

Sponsor

PrECOG, LLC.

Last update posted

Aug 17, 2026

Last verified

Aug, 2026

Keywords

Newly Diagnosed High-Risk Multiple Myeloma
Transplant Ineligible Multiple Myeloma
High-Risk Cytogenetic Multiple Myeloma
Belantamab Mafodotin
Daratumumab-Hyaluronidase
Daratumumab
Bortezomib
Lenalidomide
Decadron
Dexamethasone

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-16. This information was provided to ClinicalTrials.gov by PrECOG, LLC. on 2026-08-17. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.